ABSTRACT. Radioimmunotherapy (RIT) targeting of cancer is limited by slow blood clearance resulting in unwanted prolonged exposure of normal tissues to radioactive agents. Pre-targeted radioimmunotherapy or PRIT using bispecific agents has been shown to be superior over traditional direct conjugation in target-tonormal organ ratios. While the clinical potential for pretargeted therapy with bispecific agent formats is clear, progress has been hindered because they are often difficult to manufacture. Rockland Immunochemicals, Inc.is teaming up with Abzyme Therapeutics LLC and the Department of Radiology, University of Pittsburgh to develop bispecific nanobodies that can be used in both cancer diagnosis and pretargeted radioimmunotherapy. In phase I, bispecific recombinant nanobodies with one arm targeting cancer biomarker HER2 and another arm against Digoxigenin will be developed. Properties of the bispecific nanobody, including in vivo clearance, tumor accumulation, in-vivo stability and bioavailability and its ability to capture digoxigenylated fluorescence dyes and radionuclides will be investigated. In the Phase II, selected bispecific nanobodies will be produced in a large scale. Pharmacokinetic, pharmacodynamics, immunogenic and toxicological characteristics of agents will be investigated in pre-targeted radioimmunotherapy using animal models to obtain data necessary for filing an Investigational New Drug application